Primary Liver Cell Carcinoma Research Articles

Diagnostic and prognostic impact of cytokeratin 19 expression analysis in human tumors: a tissue microarray study of 13,172 tumors

To evaluate cytokeratin 19 (CK19) expression in normal and cancerous tissues, 15,977 samples from 122 tumor types and 608 samples of 76 normal tissue types were analyzed by immunohistochemistry (IHC). In normal tissues, CK19 expression occurred in epithelial cells of most glandular organs but was strictly limited to the basal cell layer of nonkeratinizing squamous epithelium and absent in the skin. CK19 expression in ≥90% of cases was seen in 34% of the tumor entities including the adenocarcinomas of the pancreas (99.4%), colorectum (99.8%), esophagus (98.7%), and stomach (97.7%), as well as breast cancer (90.0%-100%), high-grade serous (99.1%) or endometrioid (97.8%) ovarian cancer, and urothelial carcinoma (92.6%-100%). A low CK19 positivity rate (0.1-10%) was seen in 5 of 122 tumor entities including hepatocellular carcinoma and seminoma. A comparison of tumor versus normal tissue findings demonstrated that upregulation and downregulation of CK19 can occur in cancer and that both alterations can be linked to unfavorable phenotypes. CK19 downregulation was linked to high grade (p=0.0017) and loss of estrogen receptor- and progesterone receptor-expression (p<0.0001 each) in invasive breast carcinoma of no special type. CK19 upregulation was linked to nodal metastases in neuroendocrine tumors and papillary thyroid carcinomas (p<0.05 each) and to poor grade in clear cell renal cell carcinoma (p<0.05). CK19 upregulation was particularly common in squamous cell carcinomas. We concluded that CK19 IHC might separate primary liver cell carcinoma from liver metastases, seminoma from other testicular tumors, and helps in the detection of early neoplastic transformation in squamous epithelium.

Common Findings in Ultrasound Examination of the Liver and Kidney in Sokoto Metropolis

Objectives: To evaluate and document common findings in ultrasound examination of the liver and kidneys in Sokoto metropolis and to reveal gender and age distribution of the findings in these organs.&#x0D; Materials and Methods: The data was collected retrospectively from the hospital archives and records using a data capture sheet.&#x0D; Results: Total sample of 322 ultrasound reports of the liver and kidneys in which some patients had two findings, one in the liver and another in the kidney, some had liver findings only, some kidney findings only, while some had normal ultrasound examination. Liver findings recorded a dominant male gender with a frequency of 75 (70.1%). Findings in the liver reported were liver cirrhosis, hepatomegaly, fatty liver, primary liver cell carcinoma, hepatic metastasis, chronic liver disease (CLD), hepatitis, hepatoma and liver cyst. Liver cirrhosis had the highest frequency with 29 (27.1%), hepatomegaly with a frequency of 17 (15.9%) followed by fatty liver and plcc with a frequency of 13 (12.1%) each. The age range of 40-49 years had the highest frequency for the liver findings with 23 (21.5%), followed by 60-69 years with 18 (16.8%) while 10-19 years had the least frequency with 3 (2.8%). For the kidney findings, male gender also dominated the findings with a frequency of 107 (64.1%). The age range that had the highest frequency was 20-29 years with 43 (25.7%), followed by 30-39 years with a frequency of 27 (16.2%). The age range with the least frequency was 80-89 years with 6 (3.6%). The pathological kidney findings reported were pyelonephritis, renal parenchyma disease (grades I, II, III, and IV), hydronephrosis, renal calculi, renal cyst, ectopic kidney, renal mass, renal failure and nephrotic syndrome. Pyelonephritis was recorded as the commonest finding with a frequency of 67 (40.1%), followed by renal parenchymal disease with 35 (21.0%).&#x0D; Conclusion: The study revealed that male gender is at higher risk of having both liver and kidney diseases in Sokoto metropolis than the female and the age of those at higher risk ranged from 20-49 years.&#x0D; Liver cirrhosis and pyelonephritis are the commonest diseases of the liver and kidneys respectively.

Multiple primary cancers: Simultaneously occurring prostate cancer and other primary tumors-our experience and literature search.

Prostate cancer is a leading cause of death in men all over the world, and it is becoming an increasing public health burden in sub-Saharan Africa. In our practice, we identified that prostate cancer co-existed with other primary cancers even in noncontiguous regions of the body and this co-existence impacted on our management of these patients. We retrospectively studied a 2-year period (June 2012-July 2014), the records of patients in our hospital with prostate cancer, who in addition, had other primary cancers; and studied the management and outcomes of these patients. We also reviewed the existing literatures for possible biologic links between prostatic carcinoma and other primary tumors. There were six patients with multiple primary cancers who had prostate cancers. The age range was 60-84 years and the mean age of 72.2 ± 0.4 years. The primary tumors co-existing with prostate cancer were colonic adenocarcinoma, rectal adenocarcinoma, urinary bladder transitional cell carcinoma, primary liver cell carcinoma, and thyroid follicular carcinoma in both synchronous and metachronous relationships. Prostate cancers often co-exist with other cancers. The precise mechanism by which prostate cancer co-exists with another primary cancer is yet to be clearly defined. With more study of the syndromic cancers involving the prostate, definite associations could be identified, and this may help in managing these patients better.

English

Globally, Hepatitis B viral infection is a major epidemic and responsible for one of the commonest cancers in males reference needed because the HBsAg seroprevalence in males slightly higher than females, especially in sub-Saharan Africa. However, although its treatment is available and effective, it is out of the reach of the common person. Many have, because of cost of treatment, succumbed to the chronic effects of HBV infection, such as liver cirrhosis and primary liver cell carcinoma. In this article, we make a case for the provision of free antiviral drugs to all HBV patients by expanding the current HIV services to HBV-infected individuals using the PMTCT model. This, when implemented, will save lives, prevent unnecessary and escalating health expenditure and ensure sustainable development. Key words: Hepatitis B viral infection, HIV PMTCT, Nigeria, expanding HIV services

Tricuspid Valve Obstruction by a Tumour Thrombus in Primary Liver Cell Carcinoma

&lt;p&gt;Okeahialam B.N. Tricuspid valve obstruction by a tumour thrombus in primary liver cell carcinoma. International Cardiovascular Forum Journal. 2015;4:86-87 DOI: 10.17987/icfj.v4i0.129&lt;/p&gt;

50 Years Ago in TheJournalof Pediatrics: Primary Liver Cell Carcinoma Associated with Biliary Cirrhosis Due to Congenital Bile Duct Atresia

50 Years Ago in TheJournalof Pediatrics: Primary Liver Cell Carcinoma Associated with Biliary Cirrhosis Due to Congenital Bile Duct Atresia

Pattern of Childhood Malignancies in Ilorin, Nigeria: Challenges and Strategies for Management in a Tertiary Health Institution

Objective: The study was carried out to document the pattern of childhood malignant tumors which were diagnosed at the University of Ilorin Teaching Hospital, Ilorin, and compare with previous reports from other parts of Nigeria and elsewhere and also highlight the challenges and strategies for effective management of these diseases in our environment. Methods: A ten year retrospective analysis of all cancers diagnosed in children below the age of 18 years at the study centre between January 2000 and December 2009 was carried out. Case folders of all children diagnosed with malignant tumors within the study period were retrieved from the Cancer Registry Department of the Hospital and were analyzed with respect to age, gender, morphological or histological type of malignancy, extent of disease, treatment modality, and survival outcome. Results: Ninety nine (99) children were diagnosed with various malignancies during the study period. Sixty seven (67; 67.7%) were boys and 32 (32.3%) were girls giving a male to female ratio of 2:1. There were 22 cases (22.2%) recorded in children aged below 4 years and 72 cases (72.7%) were diagnosed in children between 4-14 years. Lymphomas were the most prevalent malignancies encountered accounting for 54 cases (54.5%), Burkitt’s lymphoma constituted 43 (79.6%) of all lymphoma cases. The distribution of the five foremost malignancies recorded were as follows: Burkitt’s lymphoma (43 cases), Nephroblastoma (10 cases), Retinoblastoma (8 cases), Non Hodgkin’s lymphoma (7 cases) and Acute leukaemias (5 cases). Other malignancies included Osteogenic sarcoma (5), Hodgkin’s lymphoma (4), and 2 cases each of primary liver cell carcinoma, neuroblastoma, rhabdomyosarcoma and nasopharyngeal tumor. Conclusion: The distribution of the various childhood malignant tumors recorded in this study is similar to the pattern reported in previous studies from Nigeria and other countries. However, there appears to be a lower prevalence of leukemia recorded in this study compared to the earlier findings. The challenges which were identified in the diagnosis, management and overall outcome of our patients included limited number of diagnostic tools, late presentation in the hospital, high patient default rate, poverty, and shortage of chemotherapeutic drugs.Bangladesh Journal of Medical Science Vol.14(3) 2015 p.241-246

Medical causes of death in a teaching hospital in South-Eastern Nigeria: A 16 year review.

Most developing regions of the world are undergoing gradual epidemiological transition resulting in high burden of both communicable and noncommunicable diseases. This affects the pattern of death in this region. The objective of this study is to determine the causes of death in the medical wards of the University of Nigeria Teaching Hospital, Ituku/Ozalla, Enugu, South-East Nigeria from 1995 to 2010. Data were collected retrospectively from January 1995 to December 2010. Statistical Package for Social Sciences (SPSS Inc. Chicago, IL, USA) version 17.0 was used. Simple descriptive statistics were done. Student's t-test was used to compare means of continuous variables, while Chi-square test was used to test significance of differences between two proportions. The mortality rate was 22.8% (6250/27,514) admissions. The male to female ratio was 1.7:1. Infections (20.2%) were the most common cause of death. However, chronic kidney disease was the single most common disease entity causing death (12.3%). Other important causes of death in order of prevalence were cerebrovascular accident (10.5%), acquired immune deficiency syndrome and tuberculosis either alone or as co-infection (10.3%), heart failure (8.8%), chronic liver disease (7.0%), septicemia (6.5%), respiratory failure (5.3%), diabetes mellitus (4.6%), cardiac arrhythmias (2.9%), and primary liver cell carcinoma (2.7%). There were few deaths from tetanus, malaria, typhoid fever, and coronary artery disease. Mortality is high in our medical wards and reflects the emerging trend of mixed disease spectrum comprising communicable and noncommunicable diseases.

Connective tissue growth factor (CTGF/CCN2) in serum is an indicator of fibrogenic progression and malignant transformation in patients with chronic hepatitis B infection

Still a challenging medical problem is the non-invasive monitoring of patients with a variety of chronic liver diseases being on risk to develop fibrosis, cirrhosis, and, finally, primary liver cell carcinoma. Previously, we have shown that CTGF/CCN2, a down-stream mediator of TGF-β, in serum might be a promising non-invasive biomarker of fibrosis, which is extended in the following study to cirrhosis and liver cell carcinoma.Healthy individuals (n=56), as well as fibrotic (n=77), cirrhotic (n=17), and HCC-patients (n=72) with chronic hepatitis B (HBV) infection, clinically, biochemically and histopathologically well characterized and classified, were included for the measurements of CTGF-concentrations in serum using a newly developed CTGF-enzyme immunoassay.A statistical significant increase of the mean serum CTGF-concentrations was associated with different stages of fibrosis, ranging from 15.9μg/L (S0), 20.3μg/L (S1/2) to 36.9μg/L (S3/4). The highest CTGF-concentrations were measured in cirrhotic patients (43.6μg/L), compared to healthy subjects (17.7μg/L), followed by a decrease in cirrhotic HCC-patients (38.5μg/L; p=0.001). Of note, HCC patients without underlying cirrhosis (n=8) had CTGF levels (13.5±13.2μg/L) comparable to those in healthy controls. No statistical relation between CTGF levels and parameters of liver injury (e.g. AST, ALT) was noticed, but CTGF levels are correlated negatively with serum albumin levels (p=0.007) and platelet counts (p=0.0032), respectively. The latter was negatively correlated with the stage of fibrosis (p=0.025). In HCC patients, CTGF concentrations decreased with tumor progression and size, with lower levels in TNM stage II (30.5μg/L) and stage III (33.6μg/L) compared to TNM stage I (41.6μg/L).Our data suggest a valuable diagnostic impact of CTGF in serum for the follow-up of patients suffering from chronic liver diseases developing fibrosis, cirrhosis and finally HCC. CTGF serum levels in HCC are most likely due to underlying fibrosis/cirrhosis but not due to malignancy per se.

Pattern of cancer deaths in the medical wards of a teaching hospital in South East Nigeria

Cancers are emerging public health problems in developing countries like Nigeria. The epidemiological shift and aging population make cancers a challenge. We set out to describe the pattern of death due to cancer in our medical ward. The hospital is one of the premier hospitals covering the South East zone of Nigeria. We retrospectively reviewed the case notes and death certificates of all who died of cancer in our adult medical wards for 16 years (January 1995 to December 2010). Statistical Package for Social Sciences (SPSS Inc. Chicago, IL) version 17.0 was used. Twenty seven thousand, five hundred and fourteen patients were admitted into the medical wards. Six thousand, two hundred and fifty died. Out of the 6250 deaths, cancers accounted for 7.6%. Male to Female ratio was 2.4:1. The mean age at death was 43.7 ± 17.4 years. The mean age at death in both sexes was similar (42.9 ± 17.5 for men and 45.7 ± 17.0 years for women), P = 0.109. Primary liver cell carcinoma was the most common cause of death among men (40.8%), while cancer of hematopoietic organ was the most common in women (48.7%). The overall fatality rate was 1.7% (477/27 514) of medical admissions. Younger and middle age groups were most commonly affected in both sexes. Since the most productive age groups were affected, governments in developing countries should as a matter of urgency put in place adequate cancer preventive and curative services.

Seroprevalence of antibody to HDV in Nigerians with hepatitis B virus-related liver diseases.

Hepatitis D Virus (HDV) infection has been reported to be declining in some geographical areas. In order to ascertain the current status of HDV infection in Nigeria, a study of patients with hepatitis B virus (HBV)-related liver diseases was undertaken to determine the sero-prevalence ofanti-HDV. This was a prospective, cross-sectional study in which all consecutive patients with liver disease who tested positive for Hepatitis B surface antigen (HBsAg) were also tested for antibody to HDV. Ninety six patients with various forms of HBV-related liver diseases participated in the study (acute hepatitis 8.3%, asymptomatic infection 15.6%, chronic hepatitis 3.1%, liver cirrhosis 21.9% and primary liver cell carcinoma 51.0%). Anti-HDV was demonstrated in 12 patients (12.5%). In patients with acute hepatitis and asymptomatic infection the prevalence was 4.3% while in patients with chronic hepatitis, liver cirrhosis and primary liver cell carcinoma, the prevalence was 15%. HDV still contributes to significant morbidity and mortality in HBV-related liver diseases in Nigeria. There is urgent need for larger studies on a national scale to accurately appraise the public health importance of this infection.

Cutaneous features seen in primary liver cell (Hepatocellular) carcinoma patients at a University Teaching Hospital in Nigeria

Primary liver cell carcinoma (PLCC), predominantly hepatocellular carcinoma is a killer. In the southwestern region of Nigeria it occupies the second position, behind prostate cancer in males. Females account for about a third of diagnosed cases. Children are not spared. Over 80 % of PLCC cases present to the hospital at an advanced stage in Nigeria and some die within weeks of admission to the wards. A prospective hospital based study was carried out to determine muco-cutaneoeus features associated with the entity as a possible aid to diagnosis cutaneous features being considered a cheap tool that can help diagnosis in a developing country-at an affordable cost. 80 of 84 patients seen during the study period had data that were adequate for analysis. The age range was 18-76 years with a mean of 56.2 years. The male female ratio was 17:3 indicating that males remain the more affected gender. No skin feature was found to be specific to PLCC. Jaundice (63.75 %), pallor 43.75 %), peripheral oedema (32.50 %), palmoplantar macular hyperpigmentation (47.5 %/25.0% - plantar /palmar) however were the common features documented in the study. Moderate to severe pityriasis versicolor was found in 18.75 % of cases. 61.25 % had core temperature less than 36°C. Amongst non-cutaneous features found on examination, right sided upper abdominal pain/discomfort and swelling were common. While none of the features documented in this study are specific to PLCC (and most are likely related to underlying liver cirrhosis) it may be helpful to realize that Jaundice and marked palmoplantar macular pigmentation, the complaint of pain /mass, and the presence of a tender nodular mass in the right hypochondrium should make one to consider the localization of the disease to the liver. Pain/tenderness in the right hypochondrium suggest rapid growth of the liver from increased mitosis in the hepatocytes and a stretching of the liver capsule. Metastasis to the liver accounts for a very small percentage in Nigerians. A nodular liver is thus likely to be from a primary liver pathology. African Journal of Health Sciences Vol. 14 (1-2) 2007: pp. 14-18

Pathogenese und Klinik der primären Leberzellkarzinome

The hepatocellular carcinoma is the most frequent primary liver cell carcinoma. On account of its geographical distribution with preferential occurrence in China, SE Asia and South Africa, exogenic causes are thought to be mainly responsible for its aetiopathogenesis. Besides mycotoxins, the hepatitis B virus infection (HBV) is particularly important. Integration of HBV-DNS into the hepatic cell DNS is considered to be an initiatory step in hepatocarcinogenesis. Clinically the tumour usually becomes manifest by upper abdominal complaints. Curative treatment can be promising only with very small tumours which can be detected most safely via ultrasound examination and alpha-1-fetoprotein determination.

Primary liver cell carcinoma: An unusual presentation

Primary liver cell carcinoma: An unusual presentation

Serum ferritin and HCV infection on Nigerian patients with primary liver cell carcinoma

No Abstract. African Journal of Clinical and Experimental Microbiology Vol. 7(3) 2006: 149-153

DNA alkylation by 4,5-dioxovaleric acid, the final oxidation product of 5-aminolevulinic acid.

The heme precursor 5-aminolevulinic acid (ALA) accumulates under pathological conditions, namely, acute intermittent porphyria (AIP) and tyrosinosis, two diseases that are associated with increased liver cancer incidence. This has been previously linked to an enhanced production of reactive oxygen species generated by a metal-catalyzed ALA oxidation process, which was shown to cause DNA single-strand breaks and guanine oxidation within both isolated and cellular DNA. In the present work, we established that the final oxidation product of ALA, 4,5-dioxovaleric acid (DOVA), is an efficient alkylating agent of the guanine moieties within both nucleoside and isolated DNA. Adducts were produced through the formation of a Schiff base involving the N2-amino group of 2'-deoxyguanosine (dGuo) and the ketone function of DOVA, respectively. The modified dGuo nucleosides were characterized, following reduction into stable secondary amines, by extensive NMR, infrared, and mass spectrometry analyses. A method, based on the use of HPLC with electrochemical detection, was then developed for the sensitive measurement of the DOVA-dGuo adducts. Using this assay, we showed that the guanine moieties of isolated DNA can undergo the same reaction as the free nucleoside. The present data provide additional information on the genotoxic potential of ALA and reinforce the hypothesis that AIP may be involved in the induction of primary liver cell carcinoma.

5-Aminolevulinic acid induces single-strand breaks in plasmid pBR322 DNA in the presence of Fe 2+ ions

5-Aminolevulinic acid (ALA), a heme precursor accumulated in chemical and inborn porphyrias, has been demonstrated to produce reactive oxygen species upon metal-catalyzed aerobic oxidation and to cause oxidative damage to proteins, liposomes and subcellular structures. Exposure of plasmid pBR322 DNA to ALA (0.01–3 mM) in the presence of 10 μM Fe 2+ ions causes DNA single-strand breaks (ssb), revealed by agarose gel electrophoresis as an increase in the proportion of the open circular from (75 ± 7.5 at 3 mM ALA) at the expense of the supercoiled form. Addition of either anti-oxidant enzymes such as superoxide dismutase (10 μg/ml) and catalase (20 μg/ml), or a metal chelator (DTPA, 2.5 mM), or a HO . scavenger (mannitol, 100 mM) inhibited the damage (by 30, 45, 55, and 81%, respectively), evidencing the involvement of O 2 −·, H 2O 2 and HO . (by the Haber-Weiss reaction) in this process. Hydrogen peroxide (100 μM) or Fe 2+ (10 μM) alone were of little effect on the extent of DNA ssb. The present data may shed light on the correlation reported between primary liver-cell carcinoma and intermittent acute porphyria.

5-Aminolevulinic acid mediates the in vivo and in vitro formation of 8-hydroxy-2'-deoxyguanosine in DNA.

5-Aminolevulinic acid (ALA), a heme precursor accumulated in chemical and inborn porphyrias, may behave as an endogenous pro-oxidant. In chronically treated rats (40 mg ALA/kg body wt every 2 days for 15 days) the steady-state level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in liver DNA (94.5 +/- 23.3 residues/10(6) dG) was 4.5 times higher than in non-treated rats (21 +/- 7.5 residues/10(6) dG). In vitro exposure of calf thymus DNA to ALA (0.05-5 mM) in the presence of 10 microM Fe2+ caused the formation of 8-OHdG. The amount of 8-OHdG rose from 135 +/- 15 residues/10(6) dG in the control system to 1140 +/- 150 residues/10(6) dG after incubation with 5 mM ALA and 10 microM Fe2+. Diethylenetriaminepentaacetic acid (5 mM) or mannitol (100 mM) inhibited the formation of 8-OHdG by 63 and 69% respectively, evidencing the involvement of both H2O2 and HO. in this process. Hydrogen peroxide (100 microM) or Fe2+ alone did not cause DNA oxidation. The present data support the hypothesis that ALA-generated reactive oxygen species can oxidize DNA and may be involved in the development of primary liver cell carcinoma in individuals with symptomatic acute intermittent porphyria.

Surgical experience with 168 primary liver cell carcinomas treated with hepatic resection.

Liver resections were performed in 168 patients with hepatocellular carcinoma (HCC) over the past 10 years; 116 were cirrhotics. Operative mortality was 7.7% (8.6% in the cirrhotic group and 5.8% in non-cirrhotics). In the years 1987-1992 the operative mortality decreased from 15.6% to 4.9% (P < .05). A statistical analysis of survival was made with the data of 155 patients with a follow-up of more than 1 month after curative resection: 56 (36.1%) died, while 99 (63.8%) are currently alive, with a follow-up varying from 2 to 76 months. The actuarial survival rate is 56.7% after 3 years and 36.3% after 5 years (59% and 35.2% for cirrhotics; 52.2% and 37.7% for non-cirrhotics, respectively). Satisfactory results can be obtained after liver resections in HCC, even in the presence of cirrhosis. Further efforts are needed in the early diagnosis of HCC, to prevent the formation of satellite nodules and the intrahepatic tumoral spread, which represent the major cause of exclusion from surgical therapy.

EXPERIENCE OF SYNCHRONOUS DOUBLE CANCER OF THE LIVER AND OTHER ORGAN

Recently double cancer has been increasingly found with a progress of diagnostic technique for cancers. This study focused on primary liver cell carcinoma to investigate double cancer of the liver and the other organ. In 207 cases of primary liver cell carcinoma experienced at the department during a recent one decade, there were 6 cases of double cancer arising in the liver and other organ. There were 3 males and 3 females, with an average age of 69 years. All 6 patients had synchronous double cancer, and other than liver cell carcinoma they were associated with early gastric cancer in 4, lung cancer in one, and colonic cancer in one. Operative procedures for liver cell carcinomas included left lobectomy in one, partial hepatectomy in 2, excision of the tumor in one, and hepatic artery insertion in one. Simultaneous excision of both cancers could be done in only one case undergoing gastrectomy for early gastric cancer. Each one case of early gastric and lung cancer underwent excision by two-step approach. Average prognosis was 11 months. Except for one patient surviving for 28 months after operation, remaining 5 patients died of liver cell carcinoma or hepatic failure. It may be concluded that prognosis of synchronous double cancer of the liver and other organ is prescribed by that of primary hepatic cancer.